Mussel adhesive protein product and applications thereof in suppression of skin inflammations

Abstract

Disclosed are applications of a mussel adhesive protein or preparations thereof in suppression of skin inflammations. Specifically disclosed are applications of a mussel adhesive protein, preparations thereof and applications thereof in dermatitis, eczema, skin ulcer, technologies related to burns (comprising skin grafting), perniones, surgical incisions, herpes, abrasions, scars, psoriasis, erythema multiforme, skin damage after radiotherapy, skin cancers, folliculitis, urticaria and drug eruption, and applications in sunburn, polymorphous light eruption, pathological alopecia (comprising hair transplant), acne vulgaris, rosacea (that is, acne rosacea), and the like, and applications in the treatment of otitis externa.

Claims

1. A method for treating regular acne or acne rosacea, the method comprising: administering externally to the skin of an individual having regular acne or acne rosacea an effective amount of a composition comprising a mussel adhesive protein (“MAP”), wherein said skin administering treats the regular acne or acne rosacea.

2. The method according to claim 1, wherein the MAP comprises one or more of the sub-types selected from the group: Mytilus edulis foot protein (mefp) subtypes mefp-1, mefp-2, mefp-3, mefp-4, mefp-5, and mefp-6; collagens pre-COL-P, pre-COL-D, pre-COL-NG; and mussel feet matrix proteins PTMP and DTMP.

3. The method according to claim 1, wherein the MAP comprises one or more of the sub-types selected from the group mefp-1, mefp-2, mefp-3, mefp-4, mefp-5 and mefp-6.

4. The method according to claim 1, wherein the MAP comprises mefp-1.

5. The method according to claim 1, wherein the MAP is present in the composition at a concentration of 0.1 to 15.0 mg/ml.

6. The method according to claim 1, wherein the composition is a liquid formulation, a gel formulation, a lotion, a paste, or a foam formulation, or the composition is administered in the form of a therapy patch.

7. The method according to claim 1, wherein the composition has a pH in the range of 1.0 to 7.0.

8. The method according to claim 1, wherein the composition has a pH in the range of 3.0 to 6.5.

9. The method according to claim 1, wherein the composition is a medicine, a cosmetic preparation, a disinfecting product, or a healthcare product.

10. The method according to claim 1, wherein the composition is a foam formulation comprising MAP as the main active ingredient and a foaming agent matrix material, said foaming agent matrix material being one or any combination of hydroxypropylmethyl cellulose, gelatin, polyethylene glycol, sodium dodecyl sulfate, sodium fatty alcohol polyoxyethylene ether sulfonate, corn gluten powder, and acrylamide.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) FIG. 1 illustrates results of herpes zoster treatment with the MAP liquid medical device according to the present invention and the control, wherein A, patients before the treatment; B, patients at 2 weeks after the treatment.

(2) FIG. 2 illustrates the pain relief effect of the MAP liquid healthcare product according to the present invention in scar pain relief treatment.

(3) FIG. 3 illustrates the effect of the MAP liquid medical device according to the present invention in promoting wound surface healing in treatment of chronic skin ulcers, wherein A, patients at Day 0 of the treatment; B, the treatment method for the patients; C, patients at Day 7 of the treatment; D, patients at Day 10 of the treatment; E, patients at Day 15 of the treatment.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

(4) Embodiments of the present invention comprise:

(5) 1. Use of MAP in treatment of skin inflammation.

(6) 2. The use of MAP according to Embodiment 1, wherein the MAP is one or a mixture of several selected from the group consisting of subtypes mefp-1, mefp-2, mefp-3, mefp-4, mefp-5, mefp-6, the collagens pre-COL-P, pre-COL-D, pre-COL-NG, the mussel feet matrix proteins PTMP and DTMP.

(7) 3. The use of MAP according to Embodiment 1, wherein the MAP concentration may be 0.1-15.0 mg/ml.

(8) 4. The use of MAP according to Embodiment 1, wherein the MAP may be a liquid formulation, a gel formulation, a lotion, a paste, a therapy patch, or a foam formulation in use.

(9) 5. The use of MAP according to Embodiment 1, wherein MAP in the final product is in a range of pH 1.0-7.0, and in particular, in a range of pH 3.0-6.5.

(10) 6. The use of MAP according to any one of Embodiments 1-5, wherein the skin inflammation is selected from: dermatitis, eczema, skin ulcer, burn surgery (including skin grafting), frostbite, operative incision, herpes, bruise, scar, psoriasis, erythema multiforme, chemo rash, skin cancer, folliculitis, hives, and drug eruption.

(11) 7. The use of MAP according to any one of Embodiments 1-5, wherein the skin inflammation is selected from: sunburn, polymorphous sunlight eruption, pathological alopecia (including hair transplant), regular acne, and acne rosacea (i.e. brandy nose).

(12) 8. The use of MAP according to any one of Embodiments 1-5, wherein the skin inflammation is external otitis.

(13) 9. Use of MAP as an active ingredient in a composition for treatment of skin inflammation, wherein the composition is a liquid formulation, a gel formulation, a lotion, a paste, a therapy patch, or a foam formulation in use.

(14) 10. The use of MAP according to Embodiment 9, wherein the composition is a composition for external application on the skin.

(15) 11. A drug for treatment of skin inflammation, comprising MAP and a pharmaceutically acceptable carrier, wherein the MAP concentration is 0.1-15.0 mg/ml.

(16) 12. A medical device for treatment of skin inflammation, comprising MAP and a carrier acceptable in the field of medical devices, wherein the MAP concentration is 0.1-15.0 mg/ml.

(17) 13. A cosmetic for treatment of skin inflammation, comprising MAP and a carrier acceptable in the field of cosmetics, wherein the MAP concentration is 0.1-15.0 mg/ml.

(18) 14. A disinfecting product for treatment of skin inflammation, comprising MAP and a carrier acceptable in the field of disinfecting products, wherein the MAP concentration is 0.1-15.0 mg/ml.

(19) 15. A healthcare product or food for treatment of skin inflammation, comprising MAP and a carrier acceptable in the field of healthcare products or foods, wherein the MAP concentration is 0.1-15.0 mg/ml.

(20) 16. A household chemical for treatment of skin inflammation, comprising MAP and a carrier acceptable in the field of household chemicals, wherein the MAP concentration is 0.1-15.0 mg/ml.

(21) 17. Use of MAP in a drug for treatment of skin inflammation, wherein the skin inflammation is selected from: dermatitis, eczema, skin ulcer, burn surgery (including skin grafting), frostbite, operative incision, herpes, bruise, scar, psoriasis, erythema multiforme, chemo rash, skin cancer, folliculitis, hives, and drug eruption.

(22) 18. Use of MAP in a drug for treatment of skin inflammation, wherein the skin inflammation is selected from: sunburn, polymorphous sunlight eruption, pathological alopecia (including hair transplant), regular acne, and acne rosacea (i.e. brandy nose).

(23) 19. Use of MAP in a drug for treatment of skin inflammation, wherein the skin inflammation is external otitis.

(24) 20. Use of MAP in a medical device for treatment of skin inflammation, wherein the skin inflammation is selected from: dermatitis, eczema, skin ulcer, burn surgery (including skin grafting), frostbite, operative incision, herpes, bruise, scar, psoriasis, erythema multiforme, chemo rash, skin cancer, folliculitis, hives, and drug eruption.

(25) 21. Use of MAP in a medical device for treatment of skin inflammation, wherein the skin inflammation is selected from: sunburn, polymorphous sunlight eruption, pathological alopecia (including hair transplant), regular acne, and acne rosacea (i.e. brandy nose).

(26) 22. Use of MAP in a medical device for treatment of skin inflammation, wherein the skin inflammation is external otitis.

(27) 23. Use of MAP in a cosmetic for treatment of skin inflammation, wherein the skin inflammation is selected from: dermatitis, eczema, skin ulcer, burn surgery (including skin grafting), frostbite, operative incision, herpes, bruise, scar, psoriasis, erythema multiforme, chemo rash, skin cancer, folliculitis, hives, and drug eruption.

(28) 24. Use of MAP in a cosmetic for treatment of skin inflammation, wherein the skin inflammation is selected from: sunburn, polymorphous sunlight eruption, pathological alopecia (including hair transplant), regular acne, and acne rosacea (i.e. brandy nose).

(29) 25. Use of MAP in a cosmetic for treatment of skin inflammation, wherein the skin inflammation is selected from: external otitis.

(30) 26. Use of MAP in a disinfecting product for treatment of skin inflammation, wherein the skin inflammation is selected from: dermatitis, eczema, skin ulcer, burn surgery (including skin grafting), frostbite, operative incision, herpes, bruise, scar, psoriasis, erythema multiforme, chemo rash, skin cancer, folliculitis, hives, and drug eruption.

(31) 27. Use of MAP in a disinfecting product for treatment of skin inflammation, wherein the skin inflammation is selected from: sunburn, polymorphous sunlight eruption, pathological alopecia (including hair transplant), regular acne, and acne rosacea (i.e. brandy nose).

(32) 28. Use of MAP in a disinfecting product for treatment of skin inflammation, wherein the skin inflammation is external otitis.

(33) 29. Use of MAP in a healthcare product or food for treatment of skin inflammation, wherein the skin inflammation is selected from: dermatitis, eczema, skin ulcer, burn surgery (including skin grafting), frostbite, operative incision, herpes, bruise, scar, psoriasis, erythema multiforme, chemo rash, skin cancer, folliculitis, hives, and drug eruption.

(34) 30. Use of MAP in a healthcare product or food for treatment of skin inflammation, wherein the skin inflammation is selected from: sunburn, polymorphous sunlight eruption, pathological alopecia (including hair transplant), regular acne, and acne rosacea (i.e. brandy nose).

(35) 31. Use of MAP in a healthcare product or food for treatment of skin inflammation, wherein the skin inflammation is selected from: external otitis.

(36) 32. Use of MAP in a household chemical for treatment of skin inflammation, wherein the skin inflammation is selected from: dermatitis, eczema, skin ulcer, burn surgery (including skin grafting), frostbite, operative incision, herpes, bruise, scar, psoriasis, erythema multiforme, chemo rash, skin cancer, folliculitis, hives, and drug eruption.

(37) 33. Use of MAP in a household chemical for treatment of skin inflammation, wherein the skin inflammation is selected from: sunburn, polymorphous sunlight eruption, pathological alopecia (including hair transplant), regular acne, and acne rosacea (i.e. brandy nose).

(38) 34. Use of MAP in a household chemical for treatment of skin inflammation, wherein the skin inflammation is external otitis.

(39) 35. A foam formulation for treatment of skin inflammation, comprising MAP as the main active ingredient and a foaming agent matrix material, said foaming agent matrix material being one or any combination of hydroxypropyl methyl cellulose, gelatin, polyethylene glycol, sodium dodecyl sulfate, sodium fatty alcohol polyoxyethylene ether sulfonate, corn gluten powder and acrylamide, wherein the MAP concentration is 0.1-15.0 mg/ml.

(40) The present invention will be further described below with reference to specific embodiments. It should be noted that, when a drug, medical device, cosmetic, disinfecting product, healthcare product or food, or household chemical formed from MAP or various formulations of MAP according to the present invention is applied on a subject, it can be used on the indications described above and exhibits the functions described above. All formulations within the scope of the present invention have been tested, and only a small portion thereof is described below in the embodiments for the purpose of description; however, they shall not be construed as limitations to the present invention.

(41) Unless otherwise specifically described, all reagents used in the present invention are commercially available on the market.

Example 1: Use of MAP Liquid Medical Device in Treatment of Eczema

(42) Take 1 ml of an MAP solution with concentration at 20.0 mg/ml, add 9 ml of 0.1% citric acid solution, and prepare an MAP aqueous solution medical device with concentration at 2.0 mg/ml.

(43) Gather 20 patients with acute eczema as diagnosed by dermatologists for test. Eczema locations are not limited for the selected patients, the affected areas are 1-2% TBSA (total body surface area), and the affected areas have patches of erythema, dense or dispersed small papules and blisters, or large patches of weeping liquid and ulceration.

(44) For the selected patients, spray the above MAP aqueous solution medical device on the affected part, 3 times per day, and spray 3-5 times each time until the affected part is completely covered by the MAP aqueous solution medical device. After sprayed with the MAP aqueous solution medical device, itching at the affected part is significantly reduced within 2 to 10 min, the visual analogue score VAS goes from 6.0-8.0 prior to the drug administration down to 1.0-3.0, and the duration of itching relief can last 2 to 10 h (see Table 1). As the time of drug use is extended, the itching relief duration is extended, and the use interval is extended, which does not show any drug dependence.

(45) After 3 days of continuous spraying of MAP, 4 patients have their eczema areas fully healed, as indicated by disappearance of erythema, papules and blisters, and no exudation at the affected part. After 5 days of continuous spraying, all patients are cured.

(46) TABLE-US-00001 TABLE 1 Average onset time (min) 3.3 ± 1.2 Average VAS prior to use 7.6 ± 0.9 Average VAS after use 1.4 ± 0.3 Average itching relief 8.2 ± 2.1 duration (h) Average healing time (d) 3.9 ± 1.0

Example 2: Use of MAP Gel Medical Device in Treatment of Eczema

(47) Add 10 g sodium carboxymethyl cellulose into 20 ml deionized water, place in a bath at 90° C. for 30 min until complete dissolution to obtain a gel matrix. Add 2.5 ml of an MAP solution with concentration at 10.0 mg/ml into the gel matrix, add slowly under constant stirring, and mix homogeneously to form an MAP gel medical device, wherein the MAP concentration is 1.1 mg/ml.

(48) Gather 20 patients with acute eczema. Eczema locations are not specified for the selected patients, the affected areas are 1-2% TBSA (total body surface area). The patients are diagnosed by dermatologists, sign the informed consent form, and then join the clinical test. The affected areas of the patients have patches of erythema, dense or dispersed small papules and blisters, or large patches of weeping liquid and ulceration.

(49) For the selected patients, apply the above MAP gel medical device on the affected part, 3 times per day, and spray 3-5 times each time until the affected part is completely covered by the MAP gel medical device. After applied with the MAP gel medical device, itching at the affected part is significantly reduced within 1 to 7 min, the visual analogue score VAS goes from 7.0-8.0 prior to the drug administration down to 1.0-2.0, and the duration of itching relief can last 2 to 8 h. As the time of drug use is extended, the itching relief duration is extended, and the use interval is extended, which does not show any drug dependence.

(50) After 3 days of continuous application of the MAP gel medical device, 8 patients have their eczema areas fully healed, as indicated by disappearance of erythema, papules and blisters, and no exudation at the affected part. After 5 days of continuous spraying, all patients are cured (see Table 2).

(51) TABLE-US-00002 TABLE 2 Average onset time (min) 3.8 ± 2.1 Average VAS prior to use 7.7 ± 0.5 Average VAS after use 1.3 ± 0.2 Average itching relief 6.9 ± 2.1 duration (h) Average healing time (d) 3.2 ± 1.0

Example 3: Use of MAP Gel Cosmetic in Treatment of Polymorphous Sunlight Eruption

(52) Take an MAP solution with concentration at 0.5 mg/ml, mix with polyethylene glycol and glycerin at a volumetric ratio of 2:1:2, then add water for injection in an equal volume to prepare an MAP gel cosmetic, wherein the MAP content is 0.1 mg/g.

(53) Gather 10 patients with acute inflammatory reaction after sunbath, it is required that the affected parts of the selected patients include the face or limbs, and the affected areas are no smaller than 1% TBSA (total body surface area). The patients are diagnosed by dermatologists for test. The affected parts of the selected patients have erythema, edema or blisters. Apply the above MAP gel cosmetic at the affected part for 3 times per day, and evenly apply the gel on the surface of the affected part each time. After applied with the MAP gel cosmetic, mitigation of itching and pain occurs to all the 10 patients, the onset time varies from 3 to 20 min, and the itching or pain relief duration is 3-8 h after use. After applying the MAP gel cosmetic for 5 days, all the 10 patients of sunlight eruption have their affected parts healed. Erythema, edema or blisters disappear (see Table 3).

(54) TABLE-US-00003 TABLE 3 Average onset time (min) 12.6 ± 3.7 Average VAS prior to use  4.9 ± 0.8 Average VAS after use  1.1 ± 0.4 Average itching relief  5.6 ± 1.7 duration (h) Average healing time (d)  4.0 ± 0.6

Example 4: Use of MAP Lotion Medical Device in Treatment of Polymorphous Sunlight Eruption

(55) Take an MAP solution with concentration at 2.0 mg/ml, mix with propanediol and glycerin at a volumetric ratio of 1:1:2, then add water for injection in an equal volume to prepare an MAP lotion medical device, wherein the MAP content is 0.25 mg/g.

(56) Gather 10 patients with acute inflammatory reaction after sunbath, it is required that the affected parts of the selected patients include the face or limbs, and the affected areas are no smaller than 1% TBSA (total body surface area). The patients are diagnosed by dermatologists for test. The affected parts of the selected patients have erythema, edema or blisters. Apply the above MAP lotion medical device at the affected part for 3 times per day, and evenly apply the household chemical lotion on the surface of the affected part each time. After applied with the MAP lotion medical device, mitigation of itching and pain occurs to all the 10 patients, the onset time varies from 2 to 18 min, and the itching or pain relief duration is 3-10 h after use. After applying the MAP hydrogel cosmetic for 4 days, all the 10 patients of sunlight eruption have their affected parts healed. Erythema, edema or blisters disappear (see Table 4).

(57) TABLE-US-00004 TABLE 4 Average onset time (min) 10.2 ± 2.6 Average VAS prior to use  5.2 ± 1.6 Average VAS after use  1.0 ± 0.7 Average itching relief  6.6 ± 1.3 duration (h) Average healing time (d)  3.5 ± 0.7

Example 5: Use of MAP Hydrogel Medical Device in Treatment of Deep Second Degree Burn

(58) Take an MAP solution, mix with Guar gum, propanediol and propanetriol at a volumetric ratio of 4:1:1:1, add water for injection, use citric acid to adjust to pH 5.0, and prepare an MAP hydrogel medical device with the MAP content at 1.5 mg/ml.

(59) Gather 30 patients of deep second degree burn, it is required that more than two doctors jointly confirm that the patients have deep second degree burn, and the patients sign the informed consent form and then join the study. The total burn area is less than 30% TBSA (total body surface area), and the tested part has an area greater than 2% TBSA. Use the above MAP gel medical device (test group) and a commercial chitosan gel (control group) as a control to treat, randomly, the subjects. Both products are used once every other day in an amount that can evenly cover the affected part. All the wounds need to be thoroughly cleaned with a disinfectant prior to the use of the product for the test group and the control product.

(60) Observe the redness and swelling (wound edge width) of wound edges of the wounds in the test group and the control group at the same day (Day 0) of joining the study, Days 4, 6, 10, and 14, respectively, and perform analysis using the chi-square test. In the case where the test level α is 0.05, the differences on Days 10 and 14 are statistically significant (see Table 5). It is believed that the MAP hydrogel medical device according to the present invention is better than the control product in mitigating redness and swelling. At the same time, it is further observed that the MAP hydrogel medical device according to the present invention has the effect of inhibiting exudation in the acute inflammation phase of burns and lowering the probability of growth of microorganisms.

(61) TABLE-US-00005 TABLE 5 Index Test group Control group P value Day 0 0.7640 None 4 (26.67%) 5 (33.33%) Light 4 (26.67%) 2 (13.34%) Mild 3 (20.00%) 4 (26.67%) Severe 4 (26.67%) 4 (26.67%) Day 4 0.6895 None 5 (33.33%) 6 (40.00%) Light 5 (33.33%) 4 (26.67%) Mild 4 (26.67%) 1 (6.67%)  Severe 1 (6.67%)  4 (26.67%) Day 6 1.0083 None 5 (33.33%) 7 (46.70%) Light 6 (40.00%) 3 (20.00%) Mild 3 (20.00%) 2 (13.33%) Severe 1 (6.67%)  3 (20.00%) Day 10 0.0429 None 12 (80.00%)  8 (53.33%) Light 2 (13.34%) 2 (13.34%) Mild 1 (6.67%)  5 (33.33%) Severe 0 (0.00%)  0 (0.00%)  Day 14 0.0376 None 13 (86.67%)  7 (46.70%) Light 2 (13.34%) 3 (20.00%) Mild 0 (0.00%)  5 (33.33%) Severe 0 (0.00%)  0 (0.00%) 

Example 6: Use of MAP Liquid Drug in Treatment of Deep Second Degree Burn

(62) Take an MAP solution with concentration at 5 mg/ml, add 0.001% acetic acid in an equal volume to dilute to 2.5 mg/ml, the pH of the solution is 5.0, and form an MAP liquid drug with an MAP content of 2.5 mg/ml.

(63) Gather 30 patients of deep second degree burn, it is required that more than two doctors jointly confirm that the patients have deep second degree burn, and the patients sign the informed consent form and then join the study. The total burn area is less than 30% TBSA (total body surface area), and the tested part has an area greater than 2% TBSA. Use the above MAP liquid drug (test group) and a commercial chitosan liquid product (control group) as a control to treat, randomly, the subjects. Both products are used once every other day in an amount that can evenly cover the affected part. All the wounds need to be thoroughly cleaned with a disinfectant prior to the use of the product for the test group and the control product.

(64) Observe the redness and swelling (wound edge width) of wound edges of the wounds in the test group and the control group at the same day (Day 0) of joining the study, Days 4, 6, 10, and 14, respectively, and perform analysis using the chi-square test. In the case where the test level α is 0.05, the difference on Day 10 is statistically significant (see Table 6). It is believed that the MAP liquid drug according to the present invention is better than the control product in mitigating redness and swelling. At the same time, it is further observed that the MAP liquid drug has the effect of inhibiting exudation in the acute inflammation phase of burns and lowering the probability of growth of microorganisms.

(65) TABLE-US-00006 TABLE 6 Index Test group Control group P value Day 0 0.9592 None 4 (26.67%) 5 (33.33%) Light 4 (26.67%) 2 (13.34%) Mild 3 (20.00%) 4 (26.67%) Severe 4 (26.67%) 4 (26.67%) Day 4 1.0743 None 6 (40.00%) 6 (40.00%) Light 5 (33.33%) 3 (20.00%) Mild 3 (20.00%) 2 (13.34%) Severe 1 (6.67%)  4 (26.67%) Day 6 0.8739 None 7 (46.70%) 7 (46.70%) Light 5 (33.33%) 3 (20.00%) Mild 3 (20.00%) 2 (13.33%) Severe 0 (0.00%)  3 (20.00%) Day 10 0.0420 None 11 (73.33%)  8 (53.33%) Light  3 (20.00%)  2 (13.34%) Mild 1 (6.67%)  5 (33.33%) Severe 0 (0.00%)  0 (0.00%) 

Example 7: Use of MAP Liquid Medical Device in Treatment of Shingles

(66) Take an MAP solution, dilute with physiological saline, use acetic acid to adjust to pH 4.0, and obtain an MAP liquid medical device, wherein the MAP concentration is 5 mg/ml.

(67) Select 15 patients of shingles, it is required that the affected areas are greater than 1% TBSA, the patients have a pain score≥4, and they are diagnosed by dermatologists before joining the study. Spray the MAP liquid medical device above at the affected part for 4 times per day. After sprayed with the MAP liquid medical device, the feeling of pain is weakened at the affected part within 1 min, and the duration of pain relief can last for 1.8 to 3 h on the 1st day of the use of the device. After 5 days of continuous spraying, the duration of pain relief is extended to 15 h, and the use interval is extended. After 7 days of continuous spraying of the MAP liquid medical device above, erythema and blisters of shingles on 9 patients disappear, and their skin lesions heal. After 14 days, erythema and blisters disappear for the other 6 patients, and their skin lesions heal (see FIG. 1).

Example 8: Use of MAP Hydrogel Disinfecting Product in Treatment of Shingles

(68) Take an MAP solution, mix with Guar gum and propanetriol at a mass ratio of 2:1:1, dilute with physiological saline, use acetic acid to adjust to pH 4.0, and obtain an MAP hydrogel disinfecting product, wherein the MAP concentration is 5.0 mg/ml.

(69) Select 15 patients of shingles, it is required that the affected areas are greater than 1% TBSA, the patients have a pain score≥4, and they are diagnosed by dermatologists before joining the study. Apply the above MAP hydrogel disinfecting product on the affected part for 4 times per day and at a dose that can evenly cover the affected part. After sprayed with the MAP hydrogel disinfecting product, the pain at the affected part subsides within 1 to 8 min (onset time), and the duration of pain relief can last 2.2 to 5.0 h. After 5 days of continuous use, the duration of pain relief is extended to 12-15 h, and the use interval is extended. After 7 days of continuous application of the MAP hydrogel disinfecting product, erythema and blisters of shingles on 10 patients disappear, and their skin lesions heal. After 10 days, erythema and blisters disappear for the other 5 patients, and their skin lesions heal (see Table 7).

(70) TABLE-US-00007 TABLE 7 Average onset time min  6.2 ± 1.8 Average VAS prior to use  5.9 ± 1.3 Average VAS after use  1.0 ± 0.6 Average itching relief 13.6 ± 1.3 duration (h) Average healing time (d)  7.9 ± 1.4

Example 9: Use of MAP Liquid Cosmetic in Scar Pain Relief Treatment

(71) Mix an MAP solution with sodium alginate and glycerin at a ratio of 3:2:1 to prepare a formulation, use citric acid to adjust to pH 4.2, and obtain an MAP liquid drug, wherein the MAP concentration is 10 mg/ml.

(72) Select 16 patients with post-operative scar pain, there is no limitation to the position of the scars, but the scar pain score must be ≥4 (the VAS scoring method is used to score the patients' pain). The patients can join the groups for test only after being diagnosed by plastic & reconstructive surgeons. Apply the MAP liquid cosmetic above at the affected part for 1 time per day. After applied with the MAP liquid cosmetic, the pain subsides at the affected part within 3 min, and the duration of pain relief can last for 9 to 15 h on the 1st day of the drug use. After 5 days of continuous application, the duration of pain relief is extended to 48-96 h, and at the same time, inflammatory symptoms of the scars, such as redness and swelling, subside.

Example 10: Use of MAP Liquid Healthcare Product in Scar Pain Relief Treatment

(73) Take an MAP solution, mix with propanediol at a ratio of 2:1, use acetic acid to adjust to pH 4.0, and obtain an MAP liquid healthcare product, wherein the MAP concentration is 10 mg/ml.

(74) Gather 10 patients with post-operative scar pain, there is no limitation to the position of the scars, but the scar pain score must be ≥4 (the VAS scoring method is used to score the patients' pain). The patients can join the groups for test only after being diagnosed by plastic & reconstructive surgeons. The patients are randomly divided into a control group and a test group, who apply physiological saline and the above MAP liquid healthcare product, respectively, at the affected part for 1 time per day. After spraying the MAP liquid healthcare product, record pain mitigation situations at Days 0, 3, 7 and 13, for the test group, the pain decreases from 5.3 when the group begins to 0.7 after the use, and the p value is 0.017 compared with the control group that decreases from 6.1 to 3.1, which is statistically significant (α=0.05) (see FIG. 2). It proves that the MAP liquid healthcare product according to the present invention can mitigate the pain caused by shingles.

Example 11: Use of MAP Liquid Medical Device in Treatment of Operative Incisions

(75) Take an MAP solution, dilute with a borate aqueous solution to obtain an MAP liquid formulation, and the pH is 5.5, wherein the MAP concentration is 2.5 mg/ml.

(76) Gather 20 patients, whose incisions are stitched up with surgical sutures after abdominal operations, for test. The patients are diagnosed by surgeons and then join the groups. They are randomly divided into two groups, the test group is treated with the above MAP liquid medical device, and the control group is treated with physiological saline. Spray to the affected part of the selected patients at 8 h after the surgery for 4 times per day. After sprayed with the MAP liquid medical device, 10 patients keep the body positions unchanged, and the pain is mitigated significantly within 20 min, the visual analogue VAS score goes from 7.0-9.0 prior to the use down to 2.0-3.0. After sprayed with physiological saline, the visual VAS scores of the 10 patients do not change, which does not show pain suppression.

(77) The curing period of operative incisions of the 10 patients who use the MAP liquid medical device according to the present invention is 4 days, and there is no redness or swelling on the wound edge. The curing period of operative incisions of the 10 patients who use physiological saline is 6 days, and on Day 6, there is still slight redness and swelling on the wound edge (see

(78) Table 8).

(79) TABLE-US-00008 TABLE 8 Test group Control group Average onset time (min) 15.6 ± 3.7 No mitigation Average VAS prior to use  8.2 ± 1.8 8.0 ± 1.5 Average VAS after use  2.4 ± 0.5 8.0 ± 0.6 Average pain relief  8.6 ± 1.1 None duration (h) Average healing time (d)  3.9 ± 0.4 6.2 ± 0.7

Example 12: Use of MAP Hydrogel Disinfecting Product in Treatment of Operative Incisions

(80) Take an MAP solution, add carboxymethyl cellulose and glycerin at a volumetric ratio of 2:1:1, and obtain an MAP hydrogel disinfecting product, wherein the MAP concentration is 2.5 mg/ml.

(81) Gather 20 patients, whose incisions are stitched up with surgical sutures after abdominal operations, for test. The patients are diagnosed by surgeons and then join the groups. They are randomly divided into two groups, the test group is treated with the above MAP hydrogel disinfecting product, and the control group is treated with a blank gel prepared by mixing carboxymethyl cellulose and glycerin. Spray to the affected part of the selected patients at 8 h after the surgery for 4 times per day. After applied with the MAP gel disinfecting product, 10 patients keep the body positions unchanged, and the pain is mitigated significantly within 18 min, the visual analogue VAS score goes from 7.0-9.0 prior to the use down to 2.0-3.0. After applied with the blank gel, the visual VAS scores of the 10 patients do not change, which does not show pain suppression.

(82) The curing period of operative incisions of the 10 patients who use the MAP gel disinfecting product according to the present invention is 4 days, and there is no redness or swelling on the wound edge. The curing period of operative incisions of the 10 patients who use physiological saline is 6 days, and on Day 6, there is still slight redness and swelling on the wound edge (see Table 9).

(83) TABLE-US-00009 TABLE 9 Test group Control group Average onset time (min) 14.0 ± 2.9  No mitigation Average VAS prior to use 8.1 ± 1.6 8.0 ± 1.2 Average VAS after use 2.6 ± 0.8 7.8 ± 0.4 Average pain relief duration (h) 8.9 ± 1.6 None Average healing time (d) 3.5 ± 0.4 6.0 ± 0.8

Example 13: Use of MAP Liquid Medical Device in Treatment of Chronic Skin Ulcer

(84) Take an MAP freeze-dried powder, use physiological saline to prepare a 1.0 mg/ml aqueous solution, use acetic acid to adjust pH to 4.8, and obtain an MAP liquid medical device.

(85) Gather 10 patients with chronic skin ulcers caused by skin inflammation or scars, the ulcer areas are between 15 and 20 square centimeters, with manifestations of red and swollen wound edges and failure of the wound surface to heal for more than 3 months. The patients join the groups for test after being diagnosed by plastic & reconstructive surgeons. Spray the MAP liquid medical device above for the selected patients for 2 times per day. After 10 days of use, 8 patients have the redness and swelling of the wound edge mitigated. After 16 days of use, 3 patients have the wound surface healed. After 21 days of use, the remaining 10 patients have the wound surface healed (see FIG. 3).

Example 14: Use of MAP Lotion Disinfecting Product in Treatment of Chronic Skin Ulcers

(86) Take an MAP solution, mix with propanetriol at a ratio of 1:1, use acetic acid to adjust to pH 4.8, and obtain an MAP lotion disinfecting product.

(87) Gather 10 patients with chronic skin ulcers caused by skin inflammation or scars, the ulcer areas are between 15 and 20 cm.sup.2, with manifestations of red and swollen wound edges and failure of the wound surface to heal for more than 3 months. The patients join the groups for test after being diagnosed by plastic & reconstructive surgeons. Spray the MAP lotion disinfecting product above for the selected patients for 2 times per day. All 10 patients have the chronic skin ulcers healed with an average healing time of 20.2±3.7 days. The wound base is covered by new epithelial tissues with no exudation at the surface.

Example 15: Use of MAP Mask Cosmetic in Treatment of Coarse Pores

(88) Mix an MAP solution with Carrageenan and agar at a ratio of 2:2:1 to obtain an MAP mask stock solution, wherein the MAP concentration is 2.0 mg/ml. Take 20 ml of the MAP mask stock solution, and form an MAP mask cosmetic on silk paper.

(89) Gather 15 patients who have coarse pores due to the use of color makeup, environmental pollution and other reasons, and who are diagnosed by dermatologists to have coarse pores. They have the manifestation of coarse pores and characterizations of inflammation, such as slight redness and swelling in the surrounding area.

(90) Use the above MAP mask cosmetic once every other day, apply continuously for 25 min and then take it away, for a total of 10 times of use. On Day 7 of the application, the slight redness and swelling surrounding the pores are mitigated for all patients, and on Day 20, the pores shrink to normal, and there is no characterization of inflammation.

Example 16: Use of MAP Mask Medical Device in Treatment of Coarse Pores

(91) Take a 1.0 mg/ml MAP solution as a mask stock solution, take 20 ml of the MAP mask stock solution, and form an MAP mask medical device on silk paper.

(92) Gather 10 patients who have coarse pores due to the use of color makeup, environmental pollution and other reasons, and who are diagnosed by dermatologists to have coarse pores. They have the manifestation of coarse pores and characterizations of inflammation, such as slight redness and swelling in the surrounding area.

(93) Use the above MAP mask medical device once per day, apply continuously for 25 min and then take it away, for a total of 10 times of use. On Day 6 of the application, the slight redness and swelling surrounding the pores are mitigated for all patients, and on Day 18, the pores shrink to normal, and there is no characterization of inflammation.

Example 17: Use of MAP Patch Medical Device in Treatment of Drug Rash (Dermatitis Medicamentosa)

(94) Take an MAP solution, mix with polyvinyl alcohol, Guar gum, polyethylene glycol, and glycerin at a ratio of 2:1:1:0.2:0.2, use acetic acid to adjust to pH 6.5, and prepare an MAP patch stock solution, wherein the MAP concentration is 3.5 mg/ml. Take 25 ml of the MAP patch stock solution to combine with a non-woven fabric to form an MAP patch medical device.

(95) Gather 24 patients of drug rash, the affected area is greater than 1% of the body surface area and the manifestation is red papules. All patients are diagnosed by dermatologists, fill up an informed consent form and then join the study. Use the above MAP patch medical device once per day, apply continuously for 30 min and then take it away. On Day 1 of the application, the itchy degree of the affected parts of the 24 patients begins to subside, and the visual analogue VAS score goes from 6.0-9.0 down to 2.0-3.0.

(96) After 7 days of use, 8 patients have red papules completely disappeared. After 21 days of use, the remaining 16 patients have red papules completely disappeared (see Table 10).

(97) TABLE-US-00010 TABLE 10 Average VAS prior to use 8.1 ± 1.5 Average VAS after use 2.4 ± 0.6 Average healing time (d) 17.9 ± 2.4 

Example 18: Use of MAP Liquid Cosmetic in Treatment of Drug Rash (Dermatitis Medicamentosa)

(98) Take an MAP solution, use acetic acid to adjust to pH 6.0, and obtain an MAP liquid cosmetic, wherein the MAP concentration is 1.5 mg/ml.

(99) Gather 10 patients of drug rash, the affected area is greater than 1% of the body surface area and the manifestation is red papules. All patients are diagnosed by dermatologists, fill up an informed consent form and then join the study. Apply the MAP liquid cosmetic above 1 time in the morning and 1 time in the evening every day. On Day 1 of the use, the itchy degree of the affected parts of the 10 patients begins to subside, and the visual analogue VAS score goes from 7.0-9.0 down to 2.0-3.0. After 8 days of use, 5 patients have red papules completely disappeared. After 17 days of use, the remaining 5 patients have red papules completely disappeared (see Table 11).

(100) TABLE-US-00011 TABLE 11 Average VAS prior to use  8.6 ± 1.9 Average VAS after use  2.3 ± 0.8 Average healing time (d) 13.5 ± 2.7

Example 19: Use of MAP Liquid Medical Device in Treatment of Psoriasis

(101) Take an MAP solution, use acetic acid to adjust to pH 5.0, and obtain an MAP liquid medical device, wherein the MAP concentration is 1.5 mg/ml.

(102) Gather 10 patients of psoriasis, the affected area is greater than 2% of the body surface area, and the manifestation is erythema with clear boundaries and various shapes and sizes, which are surrounded by inflammatory flush. There is slight infiltration and thickening, and the surface is covered by multiple layers of silver-white scales. It is easy to scratch off the scales, and when the scales are cleaned off, there is a translucent thin film that is light red and bright. If the thin film is broken, slight bleeding can be observed. All patients are diagnosed by dermatologists, fill up an informed consent form and then join the study. Use the MAP liquid medical device above for 3 times per day. On Day 1 of the use, the itchy degree of the affected parts of the 10 patients begins to subside, and the visual analogue VAS score goes from 6.0-7.5 down to 2.0-3.0. After 10 days of use, 3 patients have erythema completely disappeared. After 20 days of use, the remaining 7 patients have erythema completely disappeared (see Table 12).

(103) TABLE-US-00012 TABLE 12 Average VAS prior to use  7.0 ± 0.5 Average VAS after use  2.4 ± 0.7 Average healing time (d) 16.4 ± 3.1

Example 20: Use of MAP Gel Drug in Treatment of Psoriasis

(104) Take an MAP solution, mix with Carbomer, Carrageenan and propanetriol at a mass ratio of 1:2:1:1, use acetic acid to adjust to pH 5.0, and obtain an MAP gel drug, wherein the MAP concentration is 1.0 mg/ml.

(105) Gather 10 patients of psoriasis, the affected area is greater than 2% of the body surface area, and the manifestation is erythema with clear boundaries and various shapes and sizes, which are surrounded by inflammatory flush. There is slight infiltration and thickening, and the surface is covered by multiple layers of silver-white scales. It is easy to scratch off the scales, and when the scales are cleaned off, there is a translucent thin film that is light red and bright. If the thin film is broken, slight bleeding can be observed. All patients are diagnosed by dermatologists, fill up an informed consent form and then join the study. Apply the MAP gel drug above for 3 times per day. On Day 1 of the use, the itchy degree of the affected parts of the 10 patients begins to subside, and the visual analogue VAS score goes from 6.5-7.8 down to 2.0-3.0. After 13 days of use, 5 patients have erythema completely disappeared. After 20 days of use, the remaining 5 patients have erythema completely disappeared (see Table 13).

(106) TABLE-US-00013 TABLE 13 Average VAS prior to use  7.1 ± 0.6 Average VAS after use  2.3 ± 0.9 Average healing time (d) 15.6 ± 2.7

Example 21: Use of MAP Liquid Medical Device in Treatment of Seborrheic Dermatitis

(107) Take an MAP solution, use acetic acid to adjust to pH 5.0, and obtain an MAP liquid medical device, wherein the MAP concentration is 1.5 mg/ml. Pour the product into a pressure comb that can store liquids, and use the pressure comb to apply the MAP liquid medical device onto the scalp.

(108) Gather 10 patients of seborrheic dermatitis, there is no limitation to the area of affected parts. The early manifestation is inflammatory papules around follicles. Subsequently as the disease develops, they become dark red patches that have relatively clear boundaries and are slightly yellow, which are covered by greasy scales or crusts. The patients feel slightly itching. All patients are diagnosed by dermatologists and then join the study. Use the MAP liquid medical device above for 3 times per day.

(109) On Day 1 of the use, the itchy degree of the affected parts of the 10 patients begins to subside, and the visual analogue VAS score goes from 6.0-7.5 down to 2.0-3.0. After 10 days of use, 3 patients have erythema completely disappeared. After 20 days of use, the remaining 7 patients have erythema completely disappeared (see Table 14).

(110) TABLE-US-00014 TABLE 14 Average VAS prior to use  7.0 ± 0.5 Average VAS after use  2.4 ± 0.7 Average healing time (d) 16.4 ± 3.1

Example 22: Use of MAP Hydrogel Cosmetic in Treatment of Seborrheic Dermatitis

(111) Take an MAP solution, add carboxymethyl cellulose and Xanthan gum at a mass ratio of 2:1:1, and obtain an MAP hydrogel cosmetic, wherein the MAP concentration is 1.5 mg/ml.

(112) Gather 10 patients of seborrheic dermatitis, there is no limitation to the area of affected parts. The early manifestation is inflammatory papules around follicles. Subsequently as the disease develops, they become dark red patches that have relatively clear boundaries and are slightly yellow, which are covered by greasy scales or crusts. The patients feel slightly itching. All patients are diagnosed by dermatologists and then join the study. Use the MAP hydrogel cosmetic above for 3 times per day. On Day 5 of the use, the itching of all the affected parts of the 10 patients subside, the inflammatory papules become lighter in color, and the patch area has a shrinking tendency. After 9 days of use, all the 10 patients have seborrheic dermatitis healed, and erythema completely disappear.

Example 23: Use of MAP Liquid Medical Device in Hair Transplant

(113) Take an MAP solution, use acetic acid to adjust to pH 5.0, and obtain an MAP liquid medical device, wherein the MAP concentration is 1.0 mg/ml.

(114) Gather 10 patients of male-pattern hair loss as diagnosed by plastic & reconstructive surgeons for artificial hair transplantation. The observation area of hair transplant is 1% of the body surface area. Test group: Prior to transplantation, 5 patients use the MAP liquid medical device above, and artificial hair is transplanted after 30 min. After hair transplant, spray the MAP medical device for 2 times per day. Control group: Prior to transplantation, spray physiological saline on 5 patients as the control, and after hair transplant, spray physiological saline for 2 times per day.

(115) For the patients in the test group that use the MAP liquid medical device according to the present invention, the percent of successful hair transplant area in the overall hair transplant area is 95.1%±2.2%; for the patients in the control group that use physiological saline, the percent of successful hair transplant area in the overall hair transplant area is 72.8%±1.7%. It shows that MAP increases the success rate of hair transplant.

Example 24: Use of MAP Liquid Medical Device in Skin Grafting

(116) Take an MAP solution, use acetic acid to adjust to pH 5.5, and obtain an MAP liquid medical device, wherein the MAP concentration is 1.2 mg/ml.

(117) Gather 10 patients of degree III burns as diagnosed by burn surgeons, and use the autologous skin grafting for treatment. The observation area of skin grafting is 1% of the body surface area. Test group: Prior to skin grafting, 5 patients use the MAP liquid medical device above, and autologous particulate skin is grafted after 3 min. After skin grafting, spray the MAP medical device again, and provide a protection by covering after 3 min. Control group: Prior to skin grafting, spray physiological saline on 5 patients as the control, and after skin grafting, spray physiological saline again. Provide a protection by covering after 3 min.

(118) For the patients in the test group that use the MAP liquid medical device according to the present invention, the percent of successful skin grafting area in the overall skin grafting area is 89.3%±1.9%; for the patients in the control group that use physiological saline, the percent of successful skin grafting area in the overall skin grafting area is 62.4%±3.2%. It shows that MAP increases the success rate of skin grafting.

Example 25: Use of MAP Liquid Medical Device in Male-Pattern Hair Loss

(119) Take an MAP solution, use acetic acid to adjust to pH 4.5, and obtain an MAP liquid medical device, wherein the MAP concentration is 1.0 mg/ml.

(120) Gather 10 patients of male-pattern hair loss as diagnosed by dermatologists. The manifestations include excess sebum secretion on the scalp, partial follicular necrosis, medium hair loss, and a need to wash hair every day.

(121) Select 3 cm.sup.2 to count the number of follicles before using the product. Wash the hair, use the MAP liquid medical device above for the 1st time, 2 times per day, and for each time, evenly spray to the entire scalp, and use continuously for 90 days. Chief complaints of the 10 patients: after the 1st time use, the sebum secretion decreases, and it is no longer necessary to wash hair every day. The product has an effect on controlling the oil. After 90 days of continuous use, count the number of follicles in the selected area again, and the number of follicles is increased by 35%±2.3%.

(122) It shows that the MAP product can, on one hand, inhibit the excess sebum secretion in male-pattern hair loss, and on the other hand, repair dying follicles and treat hair loss.